Endometrial stromal tumors of the uterus encompass a spectrum of neoplasms that can present a number of diagnostic challenges. Difficulties in the diagnosis of these tumors arise from controversies in the classification of these tumors, the occasional confusion of endometrial stromal tumors with non-stromal sarcomas, and the uncertain relationships of different tumor types within this group of neoplasms.
Stromal nodules fall at the benign end of spectrum containing these tumors. These neoplasms are circumscribed tumors composed of cells resembling those of normal mesenchymal tissue that lies between the epithelial lining and the underlying myometrium of the normal uterus, as this tissue appears during the proliferative phase of the menstrual cycle. Endometrial stromal sarcomas (ESSs) are malignant neoplasms that have traditionally been classified into low grade and high grade types. Histologically, low grade ESSs are identical to stromal nodules except for infiltration of the myometrium or vascular invasion. Accurate discrimination of stromal sarcoma from low grade ESS may therefore require extensive examination of the uterus that can only be accomplished after hysterectomy. Furthermore, the propensity of low grade ESSs to invade vessels sometimes leads to misdiagnoses as endolymphatic leiomyomatosis, a neoplasm of smooth muscle.
High grade ESSs were formerly separated from low grade ESSs by an increased frequency of mitoses (>ten per high power microscopic field) and were generally assumed to have a worse prognosis. More recently, it has been argued that the number of mitoses within ESSs is largely irrelevant to outcome, which is said to be almost exclusively a function of stage at diagnosis. Experts holding to this view place all ESSs in the same diagnostic category regardless of mitotic activity and use the term undifferentiated uterine sarcoma (UUS) for those stromal tumors that depart significantly in histologic appearance from normal endometrial stroma. Whether UUSs evolve from ESSs is unknown. UUSs are more likely to metastasize than are ESSs, but metastatic lesions from endometrial stromal tumors of any histologic subtype can cause diagnostic problems, especially if they are detected some time after removal of the uterus for benign disease.
Diagnosis and classification of endometrial stromal tumors has until now been based primarily on histologic criteria. In recent years, specific genetic alterations identified in different types of human tumors have become useful markers that have improved the accuracy of tumor diagnosis and classification. Additionally, the discovery of genetic abnormalities in tumors has also led to insights into the basic biology of normal and neoplastic tissues, and increasingly to rational forms of cancer therapy (reference Her 2/neu, p53 virus, and bcr-abl therapy).